title: Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: a microdialysis study.
abstract: OBJECTIVE
  To analyze the effect of tight glycemic control with the use of intensive insulin therapy on cerebral glucose metabolism in patients with severe brain injury.
  
  
  METHODS
  Retrospective analysis of a prospective observational cohort.
  
  
  METHODS
  University hospital neurologic intensive care unit.
  
  
  METHODS
  Twenty patients (median age 59 yrs) monitored with cerebral microdialysis as part of their clinical care.
  
  
  METHODS
  Intensive insulin therapy (systemic glucose target: 4.4-6.7 mmol/L [80-120 mg/dL]).
  
  
  RESULTS
  Brain tissue markers of glucose metabolism (cerebral microdialysis glucose and lactate/pyruvate ratio) and systemic glucose were collected hourly. Systemic glucose levels were categorized as within the target "tight" (4.4-6.7 mmol/L [80-120 mg/dL]) vs. "intermediate" (6.8-10.0 mmol/L [121-180 mg/dL]) range. Brain energy crisis was defined as a cerebral microdialysis glucose <0.7 mmol/L with a lactate/pyruvate ratio >40. We analyzed 2131 cerebral microdialysis samples: tight systemic glucose levels were associated with a greater prevalence of low cerebral microdialysis glucose (65% vs. 36%, p < 0.01) and brain energy crisis (25% vs.17%, p < 0.01) than intermediate levels. Using multivariable analysis, and adjusting for intracranial pressure and cerebral perfusion pressure, systemic glucose concentration (adjusted odds ratio 1.23, 95% confidence interval [CI] 1.10-1.37, for each 1 mmol/L decrease, p < 0.001) and insulin dose (adjusted odds ratio 1.10, 95% CI 1.04-1.17, for each 1 U/hr increase, p = 0.02) independently predicted brain energy crisis. Cerebral microdialysis glucose was lower in nonsurvivors than in survivors (0.46 +/- 0.23 vs. 1.04 +/- 0.56 mmol/L, p < 0.05). Brain energy crisis was associated with increased mortality at hospital discharge (adjusted odds ratio 7.36, 95% CI 1.37-39.51, p = 0.02).
  
  
  CONCLUSIONS
  In patients with severe brain injury, tight systemic glucose control is associated with reduced cerebral extracellular glucose availability and increased prevalence of brain energy crisis, which in turn correlates with increased mortality. Intensive insulin therapy may impair cerebral glucose metabolism after severe brain injury.
authors.affiliation: Department of Neurology, Critical Care Division, Columbia University Medical Center, New York, NY, USA. mauro.oddo@chuv.ch
authors.forename: Mauro
authors.initials: M
authors.lastname: Oddo
authors.forename: J Michael
authors.initials: JM
authors.lastname: Schmidt
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Carrera
authors.forename: Neeraj
authors.initials: N
authors.lastname: Badjatia
authors.forename: E Sander
authors.initials: ES
authors.lastname: Connolly
authors.forename: Mary
authors.initials: M
authors.lastname: Presciutti
authors.forename: Noeleen D
authors.initials: ND
authors.lastname: Ostapkovich
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Levine
authors.forename: Peter
authors.initials: P
authors.lastname: Le Roux
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Mayer
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006785:Hospitals, University; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D007362:Intensive Care Units; D007427:Intracranial Pressure; D019344:Lactic Acid / Q000032:analysis; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D019289:Pyruvic Acid / Q000032:analysis; D012189:Retrospective Studies
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D019344:Lactic Acid; D019289:Pyruvic Acid; D005947:Glucose